This program consists of five specific projects dealing with aging of genetically controlled laboratory mice. Dr. Myers will determine total lifespans and incidence of pathology in C57BL/6, DBA/2, B6D2F1, CBA/Ca, and CBA/H-T6/T6 mice, with modern clean-conventional husbandry. Dr. Sprott will delineate age-dependent behavioral changes in C57BL/6, DBA/2, and B6D2F1 mice, study the roles of genotype and past experience in controlling behavioral changes, and determine effects of long-lasting behavior patterns on longevity. Dr. Beamer will evaluate neurochemical, neuroendocrine, and neurophysiological status of aging C57BL/6, DBA/2, and B6D2F1 mice, including changes in five specific regions of the brain and systemic endocrine changes. Dr. Harrison will identify tissues in which functional declines with age are intrinsically timed in C57BL/6, DBA/2, B6D2F1, and CBA mice. Drs. Murphy and Russell will determine how mutant alleles at the W-locus shorten lifespan through primary gene effects limited to hemopoietic tissue and gonads, using transplantation between (C57BL/6 times C3H)F1 minus Wx/Wv anemic sterile and congenic plus/plus normal mice.